To assess the feasibility of ZW800-1 in the intraoperative assessment of kidney and ureter perfusion during kidney transplantations (living donor nephrectomy and transplantation)
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy endpoint: Signal-to-background ratio, defined as fluorescence signal
in the kidney and ureter compared to fluorescence signal of the surrounding
tissue.
Secondary outcome
Safety and tolerability endpoint: The occurrence or absence of adverse events
following administration of ZW800-1 in patients.
Pharmacokinetic endpoint: Analysis of blood and urine samples for serum
biochemistry, hematology and pharmacokinetics.
Background summary
Donor shortage remains one of the major problems in the field of kidney
transplantation. Different methods of increasing the organ donor pool have been
proposed by the scientific community. One of these measures is pushing the
criteria of donor acceptance; more Expanded Criteria Donors (ECD) organs are
being used for transplantation. This has significantly decreased the time a
patient waits for a transplant. However, ECD organs also carry a higher risk of
early graft loss, and would benefit of reliable and real-time viability
measurements of kidney perfusion during surgery. Such measures would greatly
help surgeons in deciding whether an ECD kidney can safely be transplanted.
This would possibly reduce the considerable risk of Delayed-Graft-Function and
primary non-function of the graft, which is associated with an increased risk
of death.1
ZW800-1 is a novel zwitterionic fluorophore and is currently being studied in
CME P17.125 to investigate its feasibility in ureter visualisation in real-time
during surgery. ZW800-1 can also be used to assess kidney and ureter perfusion,
as it is exclusively renally cleared. However, very limited data are available
on the value of fluorescence imaging during transplantation surgery. Donor
organs, during procurement of the donor organs, during machine perfusion and
immediately after transplantation are perfectly suitable for implementing
fluorescent imaging. With the use of fluorescent imaging, kidney perfusion can
be assessed to determine whether renally cleared fluorophores, such as ZW800-1,
offer a reliable tool for real-time decision making during kidney donation and
transplantation.
A number of pilot experiments are needed to establish whether the methods of
fluorescence imaging are reliable and reproducible during kidney
transplantations. Pre-clinical pilot experiments on fluorescence imaging during
machine perfusion are already ongoing in collaboration with the Department of
Surgical Sciences at the University of Oxford. The current proposal focuses on
establishing a reproducible model in clinical kidney transplantation.
Study objective
To assess the feasibility of ZW800-1 in the intraoperative assessment of kidney
and ureter perfusion during kidney transplantations (living donor nephrectomy
and transplantation)
Study design
The study is an open-label pilot study consisting of 10 kidney transplantation
couples (living kidney donor and kidney recipient). Patients (living kidney
donor and kidney recipient) will be dosed with 2.5 mg ZW800-1 during surgery.
Intervention
Administration of ZW800-1 during surgery.
Study burden and risks
The risks of participation for the patients in the trial include
hypersensitivity reactions. These risks are deemed minimal. Nevertheless
precautionary measures (supervised administration by qualified staff and
availability of medical treatmentto treat hypersensitivity reactions) are in
place and these effects are generally well manageable. The burden ofthe trial
is minimal, the research will coincide with routine care and the proposed
procedures are minimally invasive. This research could possibly provide a
useful tool to enhance visualization of ureters and assess kidney perfusion
during surgery.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1) Patients > 18 years old;
2) Patient couples scheduled for a living donor nephrectomy and kidney transplantation;
3) Patients should be capable and willing to give informed consent before study specific procedures;
4) No unacceptable known cardiovascular or pulmonary disease, renal or liver dysfunction;
5) The screening ECG and laboratory test results are within normal limits, or if any are outside of normal limits they are considered to be clinically insignificant;
6) Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Exclusion criteria
1) History of a clinically significant allergy or anaphylaxis;
2) Patients who previously underwent a kidney transplantation;
3) Patients pregnant or breastfeeding, lack of effective contraception in male or female patients with reproductive potential;
4) Any condition that the investigator considers to be potentially jeopardizing the patients well-being or the study objectives.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-000985-12-NL |
| CCMO | NL65325.058.18 |